Synthesis and characterizations of biodegradable and crosslinkable poly(epsilon-caprolactone fumarate), poly(ethylene glycol fumarate), and their amphiphilic copolymer

A series of self-crosslinkable and biodegradable polymers, poly(caprolactone fumarate) (PCLF), poly(ethylene glycol fumarate) (PEGF), and their copolymer PEGF-co-PCLF, has been developed for tissue engineering applications using a novel synthesis method. The current method employs potassium carbonate (K2CO3), other than the previously reported triethylamine, as the proton scavenger. The new synthetic route is more convenient and less time-consuming to carry out, and the synthesized polymers have a much lighter color, which renders them more suitable for self-crosslinking via photo-initiation. This group of polymers are essentially copolymers of fumaryl chloride, which contains double bonds for in situ crosslinking, with poly(epsilon-caprolactone) (PCL) or/and poly(ethylene glycol) (PEG) that has a flexible chain to facilitate self-crosslinking. Both PCLF and PEGF, and their amphiphilic copolymer PEGF-co-PCLF could be self-crosslinked or photocrosslinked to produce scaffolds without the use of a crosslinking agent. Our results suggest that these polymers are potentially useful as injectable, self-crosslinkable, and photo-crosslinkable materials for diverse tissue engineering applications.     

Evaluation of thermal- and photo-crosslinked biodegradable poly(propylene fumarate)-based networks

Biodegradable networks of poly(propylene fumarate) (PPF) and the crosslinking reagent poly(propylene fumarate)-diacrylate (PPF-DA) were prepared with thermal- and photo-initiator systems. Thermal-crosslinking was performed with benzoyl peroxide (BP), which is accelerated by N,N-dimethyl-p-toluidine (DMT) and enables injection and in situ polymerization. Photo-crosslinking was accomplished with bis(2,4,6-trimethylbenzoyl) phenylphosphine oxide (BAPO), which is activated by long-wavelength UV light and facilitates material processing with rapid manufacturing techniques, such as stereolithography. Networks were evaluated to assess the effects of the initiators and the PPF/PPF-DA double bond ratio on the mechanical properties. Regardless of the initiator system, the compressive properties of the PPF/PPF-DA networks increased as the double bond ratio decreased from 2 to 0.5. BAPO/UV-initiated networks were significantly stronger than those formed with BP/DMT. The compressive modulus of the photo- and thermal-crosslinked PPF/PPF-DA networks ranged from 310 +/- 25 to 1270 +/- 286 MPa and 75 +/- 8 to 332 +/- 89 MPa, respectively. The corresponding fracture strengths varied from 58 +/- 7 to 129 +/- 17 MPa and 31 +/- 13 to 105 +/- 12 MPa. The mechanical properties were not affected by the initiator concentration. Characterization of the network structures indicated that BAPO was a more efficient initiator for the crosslinking of PPF/PPF-DA, achieving a higher double bond conversion and crosslinking density than its BP counterpart. Estimated average molecular weights between crosslinks (Mc) confirmed the effects of the initiators and PPF/PPF-DA double bond ratio on the mechanical properties. This work demonstrates the capability to control the properties of PPF/PPF-DA networks as well as their versatility to be used as an injectable material or a prefabricated implant.     

In vivo bone and soft tissue response to injectable,biodegradable oligo(poly(ethylene glycol) fumarate) hydrogels

This study was designed to assess in vivo bone and soft tissue behavior of novel oligo(poly(ethylene glycol) fumarate) (OPF) hydrogels using a rabbit model. In vitro degradation of the OPF hydrogels was also investigated in order to compare with in vivo characteristics. Four groups of OPF hydrogel implants were synthesized by alternation of crosslinking density, poly(ethylene glycol) (PEG) block length of OPF, and cell-binding peptide content. The in vitro degradation rate of OPF hydrogels increased with decreasing crosslinking density of hydrogels, which was characterized by measuring weight loss and swelling ratio of hydrogels and medium pH change. Examination of histological sections of the subcutaneous and cranial implants showed that an uniform thin circumferential fibrous capsule was formed around the OPF hydrogel implants. Quantitative evaluation of the tissue response revealed that no statistical difference existed in capsule quality or thickness between implant groups, implantation sites or implantation times. At 4 weeks, there was a very limited number of inflammatory and multinuclear cells at the implant-fibrous capsule interface for all implants. However, at 12 weeks, OPF hydrogels with PEG block length of number average molecular weight 6090+/-90 showed extensive surface erosion and superficial fragmentation that was surrounded by a number of inflammatory cells, while OPF hydrogels with PEG block length of number average molecular weight 930+/-10 elicited minimal degradation. Constant fibrous capsule layers and number of inflammatory cells were observed regardless of the incorporation of cell-binding peptide and crosslinking density of OPF hydrogels with PEG block length of number average molecular weight 930+/-90. These results confirm that the degradation of implants can be controlled by tailoring the macromolecular structure of OPF hydrogels. Additionally, histological evaluation of implants proved that the OPF hydrogel is a promising material for biodegradable scaffolds in tissue engineering.     

Injectable, in situ forming poly(propylene fumarate)-based ocular drug delivery systems

This study sought to develop an injectable formulation for long-term ocular delivery of fluocinolone acetonide (FA) by dissolving the anti-inflammatory drug and the biodegradable polymer poly(propylene fumarate) (PPF) in the biocompatible, water-miscible, organic solvent N-methyl-2-pyrrolidone (NMP). Upon injection of the solution into an aqueous environment, a FA-loaded PPF matrix is precipitated in situ through the diffusion/extraction of NMP into surrounding aqueous fluids. Fabrication of the matrices and in vitro release studies were performed in phosphate buffered saline at 37 degrees C. Drug loadings up to 5% were achieved. High performance liquid chromatography was employed to determine the released amount of FA. The effects of drug loading, PPF content of the injectable formulation, and additional photo-crosslinking of the matrix surface were investigated. Overall, FA release was sustained in vitro over up to 400 days. After an initial burst release of 22 to 68% of initial FA loading, controlled drug release driven by diffusion and bulk erosion was observed. Drug release rates in a therapeutic range were demonstrated. Release kinetics were found to be dependent on drug loading, formulation PPF content, and extent of surface crosslinking. The results suggest that injectable, in situ formed PPF matrices are promising candidates for the formulation of long-term, controlled delivery devices for intraocular drug delivery.     

Development of biodegradable and injectable macromers based on poly(ethylene glycol) and diacid monomers

Novel biodegradable injectable poly(ethylene glycol)-(PEG) based macromers were synthesized by reacting low-molecular weight PEG (MW: 200) and dicarboxylic acids such as sebacic acid or terephthalic acid. Chemical structures of the resulting polymers were confirmed by Fourier transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopy characterizations. Differential scanning calorimetry (DSC) showed that these polymers were completely amorphous above room temperature. After photopolymerization, dynamic elastic shear modulus of the crosslinked polymers was up to 1.5 MPa and compressive modulus was up to 2.2 MPa depending on the polymer composition. The in vitro degradation study showed that mass losses of these polymers were gradually decreased over 23 weeks of period in simulated body fluid. By incorporating up to 30 wt % of 2-hydroxyethyl methylmethacrylate (HEMA) into the crosslinking network, the dynamic elastic modulus and compressive modulus was significantly increased up to 7.2 and 3.2 MPa, respectively. HEMA incorporation also accelerated the degradation as indicated by substantially higher mass loss of up to 27% after 20 weeks of incubation. Cytocompatability studies using osteoblasts and neural cells revealed that cell metabolic activity on these polymers with or without HEMA was close to the control tissue culture polystyrene. The PEG-based macromers developed in this study may be useful as scaffolds or cell carriers for tissue engineering applications.     

Controlled drug release from a novel injectable biodegradable microsphere/scaffold composite based on poly(propylene fumarate)

The ideal biomaterial for the repair of bone defects is expected to have good mechanical properties, be fabricated easily into a desired shape, support cell attachment, allow controlled release of bioactive factors to induce bone formation, and biodegrade into nontoxic products to permit natural bone formation and remodeling. The synthetic polymer poly(propylene fumarate) (PPF) holds great promise as such a biomaterial. In previous work we developed poly(DL-lactic-co-glycolic acid) (PLGA) and PPF microspheres for the controlled delivery of bioactive molecules. This study presents an approach to incorporate these microspheres into an injectable, porous PPF scaffold. Model drug Texas red dextran (TRD) was encapsulated into biodegradable PLGA and PPF microspheres at 2 microg/mg microsphere. Five porous composite formulations were fabricated via a gas foaming technique by combining the injectable PPF paste with the PLGA or PPF microspheres at 100 or 250 mg microsphere per composite formulation, or a control aqueous TRD solution (200 microg per composite). All scaffolds had an interconnected pore network with an average porosity of 64.8 +/- 3.6%. The presence of microspheres in the composite scaffolds was confirmed by scanning electron microscopy and confocal microscopy. The composite scaffolds exhibited a sustained release of the model drug for at least 28 days and had minimal burst release during the initial phase of release, as compared to drug release from microspheres alone. The compressive moduli of the scaffolds were between 2.4 and 26.2 MPa after fabrication, and between 14.9 and 62.8 MPa after 28 days in PBS. The scaffolds containing PPF microspheres exhibited a significantly higher initial compressive modulus than those containing PLGA microspheres. Increasing the amount of microspheres in the composites was found to significantly decrease the initial compressive modulus. The novel injectable PPF-based microsphere/scaffold composites developed in this study are promising to serve as vehicles for controlled drug delivery for bone tissue engineering.     

Biodegradable poly(ethylene glycol) hydrogels crosslinked with genipin for tissue engineering applications

In this study amino-terminated poly(ethylene glycol) (PEG-diamine) hydrogels were crosslinked with genipin, a chemical naturally derived from the gardenia fruit. Dissolution, swelling, and PEG-genipin release properties were determined. The dissolution studies indicated that the hydrogels are water soluble, and that the dissolution rate was concentration, mass, and temperature dependent. The dissolution rates are easily tailored from 3 min to >100 days. The PEG-genipin release study indicated that the greatest release occurs within the first 24 h of immersion in water, and that incubation at 37 degrees C elicits a greater initial release than samples incubated at room temperature for all genipin concentrations. Through scanning electron microscopy it was observed that the hydrogels are porous, and surface morphology changes before and after swelling. Furthermore, smooth muscle cell (SMC) adhesion studies indicated that the PEG-genipin hydrogel is a suitable substrate for SMC seeding. Overall, the results of these studies indicate that PEG-genipin hydrogels may provide potential scaffolding for a variety of tissue engineering applications.     

Degradative properties and cytocompatibility of a mixed-mode hydrogel containing oligo[poly(ethylene glycol)fumarate] and poly(ethylene glycol)dithiol

Our laboratory is currently exploring synthetic oligo(poly(ethylene glycol)fumarate) (OPF)-based biomaterials as a means to deliver fibroblasts to promote regeneration of central/partial defects in tendons and ligaments. In order to further modulate the swelling and degradative characteristics of OPF-based hydrogels, OPF crosslinking via a radically initiated, mixed-mode reaction involving poly(ethylene glycol) (PEG)-diacrylate and PEG-dithiol was investigated. Results demonstrate that mixed-mode hydrogels containing OPF can be formed and that the presence of 20 wt.% PEG-dithiol increases swelling and decreases degradation time vs. 10 wt.% PEG-dithiol and non-thiol-containing hydrogels (20% thiol fold swelling 28.7+/-0.8; 10% thiol fold swelling 11.6+/-1.4; non-thiol 8.7+/-0.2; 20% thiol-containing hydrogels degrade within 15 days in vitro). After encapsulation, tendon/ligament fibroblasts remained largely viable over 8 days of static culture. While the presence of PEG-dithiol did not significantly affect cellularity or collagen production within the constructs over this time period, image analysis revealed that the 20% PEG-dithiol gels did appear to promote cell clustering, with greater values for aggregate area observed by day 8. These experiments suggest that mixed-mode OPF-based hydrogels may provide an interesting alternative as a cell carrier for engineering a variety of soft orthopedic tissues, particularly for applications when it is important to encourage cell-cell contact.     

Studies on poly(propylene fumarate-co-ethylene glycol) based bone cement

Poly(propylene fumarate-co-ethylene glycol) random (PPF-1) and block (PPF-2) copolymer oligomers were prepared. Comparing the setting characteristics of PPF-1 and PPF-2 with comonomer n-vinyl pyrrolidone (n-VP) and swelling characteristics of cured PPF-1 and PPF-2, lower setting temperature and setting time was observed with the former leading to higher swelling coefficient and lower cross link density in the cured PPF-1. Due to the high swelling coefficient and low setting exothermic temperature associated with PPF-1, the bone cement was prepared from PPF-1, n-VP and hydroxyapatite (HAP). The in vitro degradation studies reveal lesser weight loss and deformation of PPF-1/n-VP/HAP based cured resin in Ringer's solution and phosphate buffered saline in comparison with that of PPF-1/n-VP cured resin. Though the bone cement composite has adequate mechanical properties with HAP, the compressive strength and modulus of the composite aged in Ringer's solution and PBS reduced appreciably which is due to extensive hydration and plasticization by the PEG unit. However, the bone-binding and bond strength of the bone cement determined as the load for separation of bones was found to be similar to that of fast setting calcium phosphate-atelocollagen (5%) bone cement. The bone cement PPF-1/n-VP/HAP could be used as scaffold for correcting the bone defects.     

Synthesis and water-swelling of thermo-responsive poly(ester urethane)s containing poly(epsilon-caprolactone), poly(ethylene glycol) and poly(propylene glycol)

Thermo-responsive multiblock poly(ester urethane)s comprising poly(epsilon-caprolactone) (PCL), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) segments were synthesized. The copolymers were characterized by GPC, NMR, FTIR, XRD, DSC and TGA. Water-swelling analysis carried out at different temperatures revealed that the bulk hydrophilicity of the copolymers could be controlled either by adjusting the composition of the copolymer or by changing the temperature of the environment. These thermo-responsive copolymer films formed highly swollen hydrogel-like materials when soaked in cold water and shrank when soaked in warm water. The changes are reversible. The mechanical properties of the copolymer films were assessed by tensile strength measurement. These copolymers were ductile when compared to PCL homopolymers. Young's modulus and the stress at break increased with increasing PCL content, whereas the strain at break increased with increasing PEG content. The results of the cytotoxicity tests based on the ISO 10993-5 protocol demonstrated that the copolymers were non-cytotoxic and could be potentially used in biomedical applications.     

Characterization of DNA release from composites of oligo(poly(ethylene glycol) fumarate) and cationized gelatin microspheres in vitro

This research investigates the release of plasmid DNA from novel hydrogel composites of oligo(poly(ethylene glycol) fumarate) (OPF) and cationized gelatin microspheres (CGMS), as well as the swelling and degradation of these materials in vitro. The release of total DNA and of double-stranded DNA was measured fluorescently, and the swelling properties and polymer mass loss of the hydrogels were assessed. Further, the structural integrity of the released DNA was determined through electrophoresis. It was found that plasmid DNA can be released in a sustained fashion over the course of up to 49-140 days in vitro from hydrogels of OPF synthesized from poly(ethylene glycol) of nominal molecular weights of 10 kDa and 3 kDa, respectively, with the release kinetics depending upon the material composition and the method of DNA loading. Released DNA was predominately double-stranded DNA (dsDNA) in structure and of the open-circular conformation. The results suggest that DNA release from hydrogel composites of OPF and CGMS is dominated by the degradation of the OPF component of the gels. Electrophoresis results indicate that the released DNA retains suitable conformation for potential bioactivity over the course of at least 63 days of release. Thus, these studies demonstrate the potential of composites of OPF and CGMS in controlled gene delivery applications.     

Kinetics of poly(propylene fumarate) synthesis by step polymerization of diethyl fumarate and propylene glycol using zinc chloride as a catalyst

Diethyl fumarate and propylene glycol were reacted in the presence of a zinc chloride catalyst to synthesize poly(propylene fumarate) (PPF) over a period of 12 hours. The kinetics of the transesterification polymerization at 130°C, 150°C, and 200°C were determined by gel permeation chromatography (GPC) analysis. The initial rate of polymerization at each temperature was quantified by calculating the rate of change of the number average molecular weight (Mn). At 200°C, gelation of the PPF occurred after 4 h. GPC analysis of the reaction showed that PPF synthesized at 150°C had a higher final Mn of 4600 (±190) and a higher weight average molecular weight of 10 500 (±760) than at 130°C (n = 3). The chemical structure of the PPF was verified by NMR and FT-IR analysis. This study demonstrated that the maximum Mn of PPF by a transesterification reaction is limited due to gelation of PPF at high temperature.     

Effect of poly(ethylene glycol) molecular weight on tensile and swelling properties of oligo(poly(ethylene glycol) fumarate) hydrogels for cartilage tissue engineering.

This study was designed to determine the effect of changes in poly(ethylene glycol) (PEG) molecular weight on swelling and mechanical properties of hydrogels made from a novel polymer, oligo(poly(ethylene glycol) fumarate) (OPF), recently developed in our laboratory. Properties of hydrogels made from OPF with initial PEG molecular weights of 860, 3900, and 9300 were examined. The PEG 3900 formulation had a tensile modulus of 23.1 +/- 12.4 kPa and percent elongation at fracture of 53.2 +/- 13.7%; the PEG 9300 formulation had similar tensile properties (modulus: 16.5 +/- 4.6 kPa, elongation: 76.0 +/- 26.4%). However, the PEG 860 gels had a significantly higher modulus (89.5 +/- 50.7 kPa) and a significantly smaller percent elongation at fracture (30.1 +/- 6.4%), when compared with other formulations. Additionally, there were significant differences in percent swelling between each of the formulations. Molecular weight between crosslinks (M(c)) and mesh size were calculated for each OPF formulation. M(c) increased from 2010 +/- 116 g/mol with PEG 860 to 6250 +/- 280 g/mol with PEG 9300. Mesh size calculations showed a similar trend (76 +/- 2 A for PEG 860 to 160 +/- 6 A for PEG 9300). It was also found that these hydrogels could be laminated if a second layer was added before the first had completely crosslinked. Mechanical testing of these laminated gels revealed that the presence of an interfacial area did not significantly alter their tensile properties. These results suggest that the material properties of OPF-based hydrogels can be altered by changing the molecular weight of PEG used in synthesis and that multilayered OPF hydrogel constructs can be produced, with each layer having distinct mechanical properties.     

Kinetics of poly(propylene fumarate) synthesis by step polymerization of diethyl fumarate and propylene glycol using zinc chloride as a catalyst

Diethyl fumarate and propylene glycol were reacted in the presence of a zinc chloride catalyst to synthesize poly(propylene fumarate) (PPF) over a period of 12 hours. The kinetics of the transesterification polymerization at 130 degrees C, 150 degrees C, and 200 degrees C were determined by gel permeation chromatography (GPC) analysis. The initial rate of polymerization at each temperature was quantified by calculating the rate of change of the number average molecular weight (Mn). At 200 degrees C, gelation of the PPF occurred after 4 h. GPC analysis of the reaction showed that PPF synthesized at 150 degrees C had a higher final Mn of 4600 (+/- 190) and a higher weight average molecular weight of 10500 (+/- 760) than at 130 degrees C (n = 3). The chemical structure of the PPF was verified by NMR and FT-IR analysis. This study demonstrated that the maximum Mn of PPF by a transesterification reaction is limited due to gelation of PPF at high temperature.     

Synthesis of poly(propylene fumarate) by acylation of propylene glycol in the presence of a proton scavenger

To synthesize high molecular weight poly(propylene fumarate) (PPF), fumaryl chloride and propylene glycol were reacted in the presence of potassium carbonate, which serves as a proton scavenger. Transesterification of the resulting low molecular weight oligomer led to a polymer with greater molecular weight than those from previous reaction methods without requiring the use of a catalyst. According to two-dimensional NMR, the backbone structure of this polymer was as expected and contained no byproducts formed by acid catalyzed addition across the fumarate double bond. Kinetic studies of the transesterification showed that the molecular weight reached a final Mn of 4900 (+/-700) and Mw of 9100 (+/-1300) after 16 h, while the polydispersity index remained below 1.8 throughout the reaction. Thus the PPF synthesized by the new method is of higher molecular weight and greater purity than our previously prepared material.     

Fibroblast adhesion and proliferation on poly(ethylene glycol) hydrogels crosslinked by hydrolyzable polyrotaxane

Fibroblast culture was performed to evaluate cell adhesion and proliferation on poly(ethylene glycol) (PEG) hydrogels crosslinked by a hydrolyzable polyrotaxane. The polyrotaxane consisting of alpha-cyclodextrins (alpha-CDs) and PEG terminated by benzyloxycarbonyl (Z)-L-phenylalanine (L-Phe) via ester linkage was used as a multi-functional crosslinker in the PEG hydrogels. From the results of contact angle and small angle light scattering measurements, it was suggested that the surface and bulk structure of the PEG hydrogels were heterogeneous. Fibroblast adhesion and proliferation on the hydrogels was observed. The number of fibroblast adhesion on the hydrogels crosslinked by the polyrotaxane was proportional to contact angle values and correlation length, and was significantly higher than those crosslinked by alpha-CDs in spite of similar contact angle and correlation length. These findings suggest that the cells recognize the surface heterogeneity due to the polyrotaxane structure, and the number of cell adhesion and proliferation is controllable by the polyrotaxane content in feed.     

Erosion of biodegradable block copolymers made of poly( -lactic acid) and poly(ethylene glycol)

Biodegradable block copolymers made of poly(ethylene glycol) monomethylether (Me.PEG) and poly( -lactic acid) (PLA) were investigated for their erosion properties. Wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC) investigations prior to erosion revealed that despite the low content of crystallizable Me.PEG of 10%, Me.PEG5-PLA45 is a partially crystalline polymer. The erosion of the polymer was investigated using cylindrical polymer matrix discs with a diameter of 8mm and a height of 1.5mm. WAXD and DSC spectra obtained from eroded polymer matrix discs suggest that both polymer blocks separate completely during erosion. The crystallinity of Me.PEG5-PLA45 was found to increase during erosion, which is probably due to the improved mobility of Me.PEG inside the polymer with a progressive degree of degradation. The erosion kinetics were found to be similar to that of PLA or poly(lactic-co-glycolic acid). During erosion the polymer matrix weight of dried samples remains constant for 11 weeks after which erosion sets in rapidly. From this observation one can conclude that the impact of the relatively small Me.PEG chains on Me.PEGS-PLA45 erosion is not pronounced. This is beneficial for all those applications that require the stability of the polymer matrix and in which the Me.PEG chain is intended to bring about other effects such as the modification of the surface properties of PLA polymers.     

Effects of transforming growth factor beta1 released from biodegradable polymer microparticles on marrow stromal osteoblasts cultured on poly(propylene fumarate) substrates

Recombinant human transforming growth factor beta1 (TGF-beta1) was incorporated into microparticles of blends of poly(DL-lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) to create a delivery vehicle for the growth factor. The entrapment efficiency of TGF-beta1 in the microparticles containing 5% PEG was 40.3 +/- 1.2% for a TGF-beta1 loading density of 6.0 ng/1 mg of microparticles. For the same loading, 17.9 +/- 0.6 and 32.1 +/- 2.5% of the loaded TGF-beta1 was released after 1 and 8 days, respectively, followed by a plateau for the remaining 3 weeks. Rat marrow stromal cells showed a dose response to TGF-beta1 released from the microparticles similar to that of added TGF-beta1, indicating the activity of TGF-beta1 was retained during microparticle fabrication and after TGF-beta1 release. An optimal TGF-beta1 dosage of 1.0 ng/mL was determined through a 3-day dose response study for maximal alkaline phosphatase (ALP) activity. The TGF-beta1 released from the microparticles loaded with 6.0 ng TGF-beta1/1 mg of microparticles for the optimal dosage of TGF-beta1 enhanced the proliferation and osteoblastic differentiation of marrow stromal cells cultured on poly(propylene fumarate) substrates. The cells showed significantly increased total cell number, ALP activity, and osteocalcin production with values reaching 138,700 +/- 3300 cells/cm(2), 22.8 +/- 1.5 x 10(-7) micromol/min/cell, and 15.9 +/- 1.5 x 10(-6) ng/cell, respectively, after 21 days as compared to cells cultured under control conditions without TGF-beta1. These results suggest that controlled release of TGF-beta1 from the PLGA/PEG blend microparticles may find applications in modulating cellular response during bone healing at a skeletal defect site.     

In vitro degradation of polymeric networks of poly(propylene fumarate) and the crosslinking macromer poly(propylene fumarate)-diacrylate

Polymeric networks of poly(propylene fumarate) (PPF) crosslinked with poly(propylene fumarate)-diacrylate (PPF-DA) are currently being investigated as an injectable, biodegradable bone cement. This study examined the effect of crosslinking density, medium pH, and the incorporation of a beta-tricalcium phosphate (beta-TCP) filler on the in vitro degradation of PPF/PPF-DA. Cylindrical specimens were submerged in buffered saline at 37 degrees C and the change in weight, geometry, and compressive mechanical properties were monitored over a 52-week period. All formulations showed an initial increase in modulus and yield strength over the first 12 weeks, achieving maxima of 1307+/-101 and 51+/-3MPa, respectively, for the beta-TCP composite. PPF/PPF-DA networks with the lower crosslinking density demonstrated the greatest degradation with a 17% mass loss. Samples in the lower buffer pH 5.0 compared to physiological pH 7.4 did not show any differences in mass loss, but exhibited a faster decrease in the compressive strength over time. The beta-TCP composites maintained their mechanical properties at the level following their initial increase. These results show that the degradation of PPF/PPF-DA networks can be controlled by the crosslinking density, accelerated at a lower pH, and prolonged with the incorporation of the beta-TCP filler.     

Functionalization of poly(ethylene glycol) and monomethoxy-poly(ethylene glycol)

Simple methods are described for the substitution of poly(ethylene glycol) and monomethoxy-poly(ethylene glycol) substitution. Affinity ligands, coenzymes, or enzymes can be covalently attached to the substitution product or they can be used as liquid ionexchangers.